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Fig. 2 | Cell Communication and Signaling

Fig. 2

From: Harnessing peroxisome proliferator-activated receptor γ agonists to induce Heme Oxygenase-1: a promising approach for pulmonary inflammatory disorders

Fig. 2

Schematic pathways for rosiglitazone-induced HO-1 expression in HPAEpiCs. Rosiglitazone triggers HO-1 expression in HPAEpiCs through two distinct pathways: PPARγ-dependent and PPARγ-independent mechanisms. PPARγ-dependent pathway: rosiglitazone enhances HO-1 expression by activating a series of events, including PKCα, AMPKα, p38 MAPKα, SIRT1, Ac-PGC1α deacetylation, NCoR fragmentation, and direct binding of activated PPARγ to the HO-1 promoter’s responsive element. PPARγ-independent pathway: in this pathway, rosiglitazone-induced HO-1 expression occurs via NOX/ROS-dependent phosphorylation of c-Src/Pyk2/Akt, leading to Nrf2 activation. Nrf2 then binds to the ARE region of the HO-1 promoter, stimulating HO-1 expression. Upregulation of HO-1 exerts anti-inflammatory effects, particularly on the expression of adhesion molecules like ICAM-1 and VCAM-1, associated with monocyte/leukocyte accumulation in pulmonary resident cells challenged with LPS. These pathways are adapted from prior studies [62, 70] and represent crucial mechanisms in mitigating inflammation in the lungs

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Cell Communication and Signaling

ISSN: 1478-811X